3-Repair

Question 1

Regeneration

Answer 1

replacement of injured cells by cells of same type

Question 2

Healing

Answer 2

tissue response to a wound (usually of skin), an inflammatory process in an internal organ, or to cell necrosis in an organ incapable of regeneration; involves two processes

Question 3

two processes of healing

Answer 3

• regeneration

- scar formation (laying down of fibrous tissue

Question 4

Cell proliferation is regulated by

Answer 4

• growth factors intrinsic to the microenvironment
• cell injury
• cell death
• mechanical stress (bone)

Question 5

The most important regulator of cell growth and differentiation (healing) is:

Answer 5

prodding resting cells (G zero) to enter the cell cycle

Question 6

Stable cells:

Answer 6

• quiescent cells
• usually G0 and low rate of division
• driven into G1 and rapid proliferation
• liver, kidney, pancreas, endothelium, fibroblasts

Question 7

Labile cells

Answer 7

• always dividing
• replace dying cells
• epithelial cells of the skin, oral cavity, exocrine ducts, and GI tract; endometrium and bone marrow cells

Question 8

Permanent cells

Answer 8

• non-dividing cells
• permanently removed from cell cycle
• irreversible injury leads only to SCAR
• nerve cells, myocardium, skeletal muscle

Question 9

Stem cells

Answer 9

-prolonged self-renewal capacity and asymmetric replication (one cell retains its self-renewing capacity and the other enters a differentiation pathway)

Question 10

Embryonic stem cells (ESC)

Answer 10

• used to study differentiation signals
• make possible production of knockout mice (inactivate or delete a specific gene in an ESC and inject the ESC into a blastocyst)
• have potential for repopulation of damaged organs

Question 11

Adult stem cells (ASC)

Answer 11

more restricted differentiation capacity than ESC

• ASC exist in bone marrow and perhaps other tissues as well
• ASC are found in niches

Question 12

Hematopoietic stem cells (HSC)

Answer 12

-give rise to all lineages of blood cells and possibly neurons and hepatocytes.

Question 13

Where are stem cells found in the liver?

Answer 13

the canals of Hering
-these give rise to progenitor cells capable of differentiation into hepatocytes or biliary cells when liver injury is severe

Question 14

satellite cells

Answer 14

• found in skeletal muscle, beneath the myocyte basal lamina
• they can differentiate into myocytes after injury
• sometimes they can also become osteogenic and adipogenic

Question 15

Two major effects of Growth factors

Answer 15

• transcription of genes that were silent in resting cells

- regulate cell entry into and passage through the cell cycle

Question 16

Four pathways of extracellular signaling

Answer 16

• Autocrine: the mediator acts on the cell that secretes it
• Paracrine
• Endocrine
• synaptic

Question 17

Autocrine:

Answer 17

the mediator acts on the cell that secretes it

• cytokines on immune cells
• growth factors on epithelial cells

Question 18

paracrine;

Answer 18

mediatory affects cells in the immediate vicinity

• inflammatory cells in infection sites
• wound healing process

Question 19

endocrine signaling

Answer 19

regulatory substance (hormone) is released into the blood stream
-ex insulin from islets of langerhans

Question 20

angiogenesis

Answer 20

growth of new blood vessels

• derived from endothelial cell precursors (angioblasts) OR
• by budding from pre-existing vessels
• basement membrane degrades
• endothelial cells migrate, proliferate, and mature

Question 21

In tissues capable of regeneration, ______ is required. If this is absent, healing by scar occurs

Answer 21

an intact connective tissue scaffold

Question 22

proliferation requires summoning ____ cells into the cell cycle (primary) and _____ (secondary importance)

Answer 22

• resting or quiescent cells (G zero)

- shortening the cell cycle

Question 23

PGF

Answer 23

polypeptide growth factors

Question 24

proteoglycans and hyaluronan

Answer 24

growth factor reservoir

-binding water to ECM

Question 25

***granulation tissue

Answer 25

pink, soft, granular grossly

Question 26

Scar formation involves the loss of what two things?

Answer 26

parenchyma and ECM

Question 27

fibrosis

Answer 27

- (fibroplasia) - occurs within the granulation tissue framework (new blood vessels and loose ECM) - proliferation of fibroblasts at site of injury - deposition of ECM

Question 28

What growth factors are associated with proliferation of fibroblasts at the site of injury?

Answer 28

TGF-beta, PDGF, EGF, FGF | -cytokines also help: IL-1, TNF-alpha

Question 29

scar remodeling

Answer 29

- strengthens the tissue - METALLOPROTEINASES - produced by macrophages, neutrophils, fibroblasts as inactive precursors, in response to local factors - debris carried away by phagocytes (debridement)

Question 30

**What are the phases of cutaneous wound healing?

Answer 30

- inflammation - proliferation - maturation

Question 31

what is the simplest type of healing

Answer 31

-primary union (with apposed or sutured tissue edges)

Question 32

secondary union (or intention)

Answer 32

``` larger defect (than primary) -tissue edges do not appose each other ```

Question 33

***what is the sequence of events in wound healing?

Answer 33

- formation of blood clot - formation of granulation tissue - cell proliferation and collagen deposition - scar formation - wound contraction - connective tissue remodeling - recovery of tensile strength

Question 34

formation of the blood clot is done by what cells in what time frame?

Answer 34

neutrophils within 24 hours

Question 35

the formation of granulation tissue is more prominent in which type of union, primary or secondary?

Answer 35

secondary

Question 36

cell proliferation and collagen deposition is done by what cells in what time frame?

Answer 36

- macrophages replace neutrophil by 96 hours (metalloproteinases, from macrophages) - they then clear debris, fibrin,... and promote angiogenesis and ECM deposition

Question 37

To form a scar, granulation tissue is converted to pale, avascular tissue, when is the scar completely acellular and without inflammation?

Answer 37

by about 30 days

Question 38

wound contraction occurs within what type of wounds and are done by what type of cells?

Answer 38

- prominent in large surface wounds (secondary union) | - myofibroblasts, which resemble smooth muscle cells, are responsible for contraction and they also lay down ECM

Question 39

which enzymes are responsible for connective tissue remodeling?

Answer 39

-Matrix metalloproteinases (MMP)

Question 40

once a wound is healed, what % of its original tensile strength is present?

Answer 40

70%, by the third month

Question 41

If inadequate formation of granulation tissue or scar formation occurs:

Answer 41

- wound dehiscence | - ulceration

Question 42

What are the different types of excessive scar formation/wound healing?

Answer 42

- hypertrophic scar/keloid - exuberant granulation tissue-"proud flesh", blocks re-epithelialization and looks like ground beef - exuberant proliferation of fibroblasts (fibromatosis) - wound contracture